U.S. patent number 10,752,637 [Application Number 16/342,215] was granted by the patent office on 2020-08-25 for bis-diox(ol)ane compounds.
This patent grant is currently assigned to Cooperatie Koninklijke Cosun U.A.. The grantee listed for this patent is Koninklijke Cooperatie Cosun U.A.. Invention is credited to Cornelis Eme Koning, Robert Lazeroms, Alwin Papegaaij, Harry Raaijmakers, Antonia Urmanova.
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United States Patent |
10,752,637 |
Lazeroms , et al. |
August 25, 2020 |
Bis-diox(ol)ane compounds
Abstract
The present invention relates to new bi-functional and
polyfunctional bis-dioxolanes and bis-dioxanes. The present
inventors have established that the bis-dioxolanes and bis-dioxanes
of the invention are highly advantageous as building blocks,
cross-linking and/or coupling agents in polymer engineering. They
can be derived from biomass sources in a highly efficient manner.
The production of the present bis-dioxolanes and bis-dioxanes from
biomass has the particular advantage that it facilitates the
introduction of desired functionality in a highly flexible manner.
Hence, the present invention provides novel bi- or polyfunctional
bis-dioxolanes and bis-dioxanes, their production from renewable
(biomass) sources, as well as their use in the engineering of
polymers.
Inventors: |
Lazeroms; Robert (Sprundel,
NL), Raaijmakers; Harry (Roosendaal, NL),
Koning; Cornelis Eme (Zwolle, NL), Papegaaij;
Alwin (Kampen, NL), Urmanova; Antonia (Zwolle,
NL) |
Applicant: |
Name |
City |
State |
Country |
Type |
Koninklijke Cooperatie Cosun U.A. |
Breda |
N/A |
NL |
|
|
Assignee: |
Cooperatie Koninklijke Cosun
U.A. (Breda, NL)
|
Family
ID: |
57184331 |
Appl.
No.: |
16/342,215 |
Filed: |
October 19, 2017 |
PCT
Filed: |
October 19, 2017 |
PCT No.: |
PCT/NL2017/050685 |
371(c)(1),(2),(4) Date: |
April 16, 2019 |
PCT
Pub. No.: |
WO2018/074926 |
PCT
Pub. Date: |
April 26, 2018 |
Prior Publication Data
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Document
Identifier |
Publication Date |
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US 20190284201 A1 |
Sep 19, 2019 |
|
Foreign Application Priority Data
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Oct 19, 2016 [EP] |
|
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16194629 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
C07H
13/12 (20130101); C07D 317/22 (20130101); C07D
493/04 (20130101); C07D 407/04 (20130101); C07H
9/04 (20130101); C07H 13/10 (20130101); C07D
407/14 (20130101) |
Current International
Class: |
C07D
493/04 (20060101); C07D 317/22 (20060101); C07D
407/04 (20060101); C07D 407/14 (20060101); C07H
9/04 (20060101); C07H 13/10 (20060101); C07H
13/12 (20060101) |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
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2006000008 |
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Jan 2006 |
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WO |
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2006091902 |
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Aug 2006 |
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WO |
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2012127119 |
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Sep 2012 |
|
WO |
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2014002039 |
|
Jan 2014 |
|
WO |
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Other References
Slivkin et al., Deposited Doc. (1975), VINITI, 3260-75, 14 pp.
Avail.: VIVITI (CAS Abstract) (Year: 1975). cited by examiner .
K. Butler et al: 144. The synthesis of some galactaric (mucic) acid
derivatives, Journal of the Chemical Society, Jan. 1, 1958 (Jan. 1,
1958), p. 740, XP055323965, Letchworth; GB. ISSN: 0368-1769, DOI:
10.1039/jr9580000740. Compounds I, Id, Ie, Il; their syntheses in
Experimental part;; p. 740, paragraph 1st. cited by applicant .
Haworth W N et al: Simple Carbohydrates Containing Unsaturated
Substituents, Journal of the Chemical Society, Chemical Society,
Letchworth; GB, Jan. 1, 1946 (Jan. 1, 1946), pp. 488-491,
XP009053096, ISSN: 0368-1769, DOI: 10.1039/JR946O0OO488. Compounds
I, II, III, IV,VII and their preparation; p. 489; compounds I, II,
III, IV,VII. cited by applicant .
Scoccia J et al: unsaturated diesters of primary, secondary, and
tertiary dials derived from dimethyl (+)-tartrate and galactaric
acid, European Journal of Organic Chemistry, Wiley--V C H Verlag
GMBH & Co. KGAA, DE, No. 20, Jan. 1, 2013 (Jan. 1, 2013), pp.
4418-4426, XPO09192629, ISSN: 1434-193X. Scheme 3; p. 4420;
compounds III, IV. cited by applicant .
Database Caplus [Online]; Chemical Abstracts Service, Columbus,
Ohio, US; 1975, Slivkin, A.I.: "Unsaturated hydroxy acid esters
based on monosaccharides and their polymerization", XP002765284,
Database accession No. 1978:136873; *the whole document*. cited by
applicant.
|
Primary Examiner: Rozof; Timothy R
Attorney, Agent or Firm: N.V. Nederlandsch Octrooibureau
Shultz; Catherine A. Stegmann; Tamara C.
Claims
The invention claimed is:
1. Compound having a structure represented by formulas (Ia) and
(Ib): ##STR00013## wherein: X represents NR.sup.a; X' represents a
heteroatom or heteroatom containing group selected from --O--,
--NH-- and --NR.sup.a'--; Z and Z' independently represent
hydrogen, a straight chain or branched C.sub.1-C.sub.4alkyl or
benzyl or the moiety Z--C--Z' represents a 5-, 6-, or 7-membered
cyclic or heterocyclic group; and R, R', R.sup.a and R.sup.a'
independently represent a reactive group containing moiety
represented by the formula --(C.sub.1-C.sub.8alkyl)-Q, wherein Q
represents a reactive group and --C.sub.1-C.sub.8alkyl represents a
branched or straight chain aliphatic alkyl group comprising 1 to 8
carbon atoms.
2. Compound according to claim 1, wherein Q represents a reactive
group selected from, hydroxyl, amine, thiol, carboxyl, oxy,
ethynyl, nitril, cyanate, isocyanate, thiocyanate, isothiocyanate,
imine, imide, azide, nitrile, nitrite, nitro, nitroso, epoxide,
cyclic carbonate, oxazoline, anhydride, acrylate and
chlorotriazine.
3. Compound according to claim 1, wherein Z and Z' represent
methyl.
4. Compound according to claim 1, wherein R, R', R.sup.a and
R.sup.a' independently represent a reactive group containing moiety
represented by the formula --(C.sub.1-C.sub.6alkyl)-Q.
5. Compound according to claim 1, having the structure represented
by formula (IIa): ##STR00014##
6. Compound according to claim 1, wherein X and X' are the
same.
7. Compound according to claim 1, wherein R, R', R.sup.a and
R.sup.a' are the same.
8. Compound according to claim 1, wherein Q represents a reactive
group selected from the group consisting of epoxide and
ethenyl.
9. Compound according to claim 1, wherein X represents NR.sup.a--;
X' represents a heteroatom or heteroatom containing group
independently selected from --O--, --NH-- and --NR.sup.a'--; Z and
Z' independently represent hydrogen, a straight chain or branched
C.sub.1-C.sub.4alkyl; and R, R', R.sup.a and R.sup.a' independently
represent a reactive group containing moiety represented by the
formula --(C.sub.1-C.sub.6alkyl)-Q, wherein --C.sub.1-6 alkyl
represents a branched or straight chain aliphatic alkyl group
comprising 1 to 6 carbon atoms, and Q represents a reactive group
selected from hydroxyl, amine, thiol, carboxyl, oxy, cyanate,
isocyanate, thiocyanate, isothiocyanate, imine, imide, epoxide,
cyclic carbonate, oxazoline, anhydride and acrylate.
10. Compound according to claim 1, X represents a heteroatom or
heteroatom containing group independently selected from --O--,
--NH-- and --NR.sup.a--; X' represents a heteroatom or heteroatom
containing group independently selected from --O--, --NH-- and
--NR.sup.a'--; Z and Z' independently represent hydrogen, a
straight chain or branched C.sub.1-C.sub.2alkyl; and R, R', R.sup.a
and R.sup.a' independently represent a reactive group containing
moiety represented by the formula --(C.sub.1-C.sub.4alkyl)-Q,
wherein --C.sub.1-C.sub.4alkyl represents a branched or straight
chain aliphatic alkyl group comprising 1 to 4 carbon atoms, and Q
represents a reactive group selected from hydroxyl, amine, thiol,
carboxyl, oxy, cyanate, isocyanate, imine, imide, and
oxazoline.
11. Compound according to claim 1 having the structure represented
by formulas (IIIf) or (IIIg): ##STR00015##
12. Method of producing a compound according to formula (Ia) or
(Ib) as defined in claim 1, said method comprising the steps of a)
providing a source of a C6 aldaric acid; b) derivatization of the
C6 aldaric acid by combining the source of the C6 aldaric acid with
a lower alkyl alcohol under conditions that cause the lower alkyl
alcohol to react with the C6 aldaric acid carboxyl groups to form
lower alkyl ester moieties; c) acetalisation of the esterified C6
aldaric acid as obtained in step b) by combining it with an
acetalisation reagent, selected from the group of the compounds
having the formula Z--C(.dbd.O)--Z' and the corresponding
di-alkoxyacetals and di-alkoxyketals, wherein Z and Z' have the
same meaning as defined in relation to formulas (Ia) and (Ib),
under conditions that cause the acetalisation reagent to react with
the aldaric acid hydroxyl groups to form the corresponding
bis-dioxane or bis-dioxolane; d) conversion of the bis-dioxane or
bis-dioxolane as obtained in step c) by reaction with a hydroxyl or
amine reagent, selected from the group consisting of the compounds
of formulas Q-(C.sub.1-C.sub.8alkyl)-OH;
Q-(C.sub.1-C.sub.8alkyl)-NH.sub.2 and
Q-(C.sub.1-C.sub.8alkyl)-NH--(C.sub.1-C.sub.8alkyl)-Q, wherein Q
and C.sub.1-C.sub.8alkyl have the same meaning as defined in
relation to formulas (Ia) and (Ib), under conditions that cause the
hydroxyl or amine reagent to displace the lower alkyl groups of the
ester moieties of the bis-diox(ol)anes to form said compound
according to formula (Ia) or (Ib).
13. Method according to claim 12, wherein the C6 aldaric acid is
galactaric acid.
14. Method according to claim 12, wherein step b), wherein the
acetalisation reagent is selected from the group consisting of
formaldehyde, acetaldehyde, acetone, propanal, butanone, butanal,
cyclohexanone, benzaldehyde and the corresponding dialkoxylated,
preferably dimethoxylated, acetals or ketals thereof.
15. Method according to claim 12, wherein X and X' represent --O--
and step d) comprises: d1) combining the bis-dioxane or
bis-dioxolane with a stoichiometric excess of a hydroxyl containing
reactant having the formula Q-(C.sub.1-C.sub.8alkyl)-OH, optionally
in a suitable solvent, to produce a liquid reaction mixture; d2)
subjecting the liquid reaction mixture to conditions under which
the displacement reaction proceeds.
16. Method according to claim 12, wherein X and X' represent
--NH--, --NR.sup.a-- or --NR.sup.a'--, and step d) comprises: d1')
combining the bis-dioxane or bis-dioxolane with the amine
containing reactant selected from the group consisting of
Q-(C.sub.1-C.sub.8alkyl)-NH.sub.2 and
Q-(C.sub.1-C.sub.8alkyl)-NH--(C.sub.1-C.sub.8alkyl)-Q in a suitable
solvent, to produce a liquid reaction mixture; d2') subjecting the
liquid reaction mixture to conditions under which the displacement
reaction proceeds.
Description
FIELD OF THE INVENTION
The present invention relates to new bi-functional and
polyfunctional bis-diox(ol)ane compounds, to methods of preparing
them and the uses thereof in the production and/or modification of
polymers. The invention, more in particular concerns a new class of
bi-functional and polyfunctional bis-diox(ol)ane compounds that can
be derived from biomass in a manner that enables the introduction
of functional groups with high versatility. The presence of two
diox(ol)ane moieties in the basic structure of the molecules
confers many interesting and highly distinctive properties to the
polymer based materials they are incorporated in, e.g. to function
as polymer cross-linker.
BACKGROUND OF THE INVENTION
In the field of polymer engineering there is an ever increasing
interest in new approaches for producing polymer materials with
specific and unique (combinations of) properties, such as enhanced
thermal stability, multiphase physical responses, compatibility,
impact response, flexibility, and rigidity. One of the recent
directions regarding polymer modification is intended to reduce the
environmental impact, in particular to improve biodegradability
and/or to increase the biobased content.
One obvious way is to produce new polymers using new combinations
of existing building blocks or employing specifically developed new
biobased building blocks to bring specific properties to the
resulting polymer material.
An attractive alternative to the development of new polymers, is
the chemical modification of existing polymers. Surface and bulk
properties can be improved easily by modifying conventional
polymers. Materials produced using such techniques have attracted
considerable attention in the industrial field as they can combine
a variety of highly distinctive properties. Sometimes, balancing of
properties is needed, and this is possible only through
modification of polymers. Prime techniques for polymer
modifications are grafting, crosslinking, blending, and composite
formation.
As will be apparent for those skilled in the art, many modalities
for development of new polymers and the modification of known ones
depend on the availability of suitable bi- or polyfunctional
monomers, which are capable of being incorporated in polymer chains
and/or of forming `bridges` within and/or among polymer chains
under appropriate conditions. Although the suitability of these
monomers for a given purpose primarily depends on the presence of
functional groups capable of interacting with reactive groups
present in the polymer chains of interest, the structure of the
hydrocarbon backbone of the bi- and polyfunctional monomer equally
affects important properties. One such property is the
compatibility of the monomer with aqueous solvents and/or the
ability to be reacted in an aqueous solvent. The interest in
polymer systems that can be produced and/or processed in aqueous
solvents has rapidly increased over the past decades, as
environmental concerns have increased resistance to processes
involving the use of (large quantities of) organic solvents.
Moreover, for certain applications the use of aqueous solvent
systems may be the preferred option simply for technical/chemical
reasons.
The synthesis of bi- and polyfunctional monomers is challenging
given the reactive nature of the functional groups that need to be
incorporated and usually. Ideally `platforms` are developed that
make a variety of homofunctional and/or heterofunctional monomers
accessible in a practical and cost-effective manner. Naturally,
environmental considerations not only play a role in the production
and/or processing of polymer systems, but equally so in the
production of the monomers as starting materials. Ideally, bi- and
polyfunctional monomers are developed that are based on renewable
sources rather than on petrochemicals.
Presently known techniques at best constitute a compromise meeting
some of these demands and often only to a limited extent. Hence,
there is a strong interest in new, preferably biobased, bi- or
polyfunctional compounds that have utility in the development of
new polymer based materials and there is accordingly a desire for
new approaches for their production in an economically feasible and
flexible manner.
The present invention seeks to provide solutions to any or all of
the aforementioned objectives.
SUMMARY OF THE INVENTION
According to the present invention, this objective is met with
certain bi-functional or poly-functional bis-dioxolane and
bis-dioxane compounds having a general structure represented by the
following formulas (Ia) or I(b):
##STR00001##
Bis-dioxolanes and bis-dioxanes according to formulas (Ia) and (Ib)
can be derived from biomass sources in a highly efficient manner.
The production of these bis-dioxolanes and bis-dioxanes from
biomass according to the invention has the particular advantage
that it facilitates the introduction of desired functionality in a
highly flexible manner.
The present inventors have established that the bis-dioxolanes and
bis-dioxanes represented by formulas (Ia) and (Ib) can
advantageously be used as biobased building blocks, cross-linking
and/or coupling agents in polymer engineering, to confer highly
interesting and distinctive properties. It has been found that
compounds according to the invention generally have good
water-solubility, in particular when compared to corresponding
structures derived from petrochemical sources. For instance, a
bis-dioxolane equivalent of the known .beta.-hydroxyalkyl-amide
cross-linker available under the tradename Primid.RTM. has
significantly higher water solubility, which opens up an array of
new applications.
The molecules of the invention are characterized by a high oxygen
content and relative rigidity of the basic structure owing to the
presence of the two cyclic acetal moieties.
The present bi- or polyfunctional bis-dioxolanes and bis-dioxanes,
to the best knowledge of the inventors, have never been disclosed
in the art before.
WO2006/091902 discloses the conversion of aldaric acids into
certain bifunctional amide derivatives, which are said to have
utility as a monomer or polymer cross-linker. The same or a very
similar concept is discussed in WO2012/127119. This document also
discloses the use of the resulting aldaric acid (di)allylamide
derivatives for cross-linking functionalized polysaccharides to
produce hydrogels.
Hence, the present invention provides novel bi- or polyfunctional
bis-dioxolanes and bis-dioxanes, their production from renewable
(biomass) sources, as well as their use in the engineering of
polymers. These and other aspects will be described and illustrated
in more detail here below.
DETAILED DESCRIPTION
A first aspect of the invention concerns bis-dioxolanes and
bis-dioxanes having a structure represented by formula (Ia) or
(Ib):
##STR00002## wherein X represents a heteroatom or heteroatom
containing group independently selected from --O--, --NH-- and
--NR.sup.a--; X' represents a heteroatom or heteroatom containing
group independently selected from --O--, --NH-- and --NR.sup.a'--;
Z and Z' independently represent hydrogen, a straight chain or
branched C.sub.1-C.sub.4alkyl or benzyl or the moiety Z--C--Z'
represents a 5-, 6-, or 7-membered cyclic or heterocyclic group;
and R, R', R.sup.a and R.sup.a' independently represent a reactive
group containing moiety represented by the formula
--(C.sub.1-C.sub.8alkyl)-Q, wherein Q represents a functional group
and --C.sub.1-8alkyl represents a branched or straight chain
aliphatic alkyl group comprising 1 to 8 carbon atoms.
The terms `bis-dioxolane` and `bis-dioxane` is used herein to
denote the compounds of the invention, because of the
characteristic structural feature common to all compounds of the
invention, notably the presence of two neighbouring 1,3-dioxolane
moieties or two fused 1,3-dioxane moieties respectively, which may
be (further) substituted. Furthermore, the terms `bifunctional` and
`polyfunctional` are used herein to indicate that the compounds
comprise two or more than two functional groups, more in particular
two or more than two reactive groups, respectively. As will be
evident from the definition above, the compounds contain at least
two such functional groups at the positions represented by R and R'
in the structure of formulas (Ia) and (Ib) and additional
functional groups may be present if X and/or X' represents
--NR.sup.a-- and --NR.sup.a'-- respectively. Hence the consistent
reference in this document to bi-functional as well as
polyfunctional bis-dioxolanes and bis-dioxanes. For ease of
reference, the compounds of the present invention, may also
collectively be referred to herein as the `bifunctional or
polyfunctional bis-diox(ol)anes` or simply as the
`bis-diox(ol)anes`.
As will be recognized by those skilled in the art, based on the
definition of formulas (Ia) and (Ib) herein, it is envisaged that
bis-dioxolanes and bis-dioxanes can be provided comprising
different heteroatoms and/or different functional groups at the
respective positions within the structure. In certain embodiments
of the invention, the bis-dioxolane and bis-dioxane compounds have
symmetrical structures, Hence in certain embodiments of the
invention compounds as defined herein are provided, wherein X and
X' are the same. Furthermore, in certain embodiments of the
invention compounds as defined herein are provided, wherein R, R',
R.sup.a and R.sup.a' are the same. In certain embodiments X and X'
are the same and R, R', R.sup.a and R.sup.a' are the same.
In certain embodiments of the invention, X and X' in formulas (Ia)
and (Ib) as defined herein represent --O-- or --NH--, preferably
they represent --NH--.
Furthermore, in certain embodiments of the invention Z, in the
above formulas (Ia) and (Ib), represents methyl.
In certain embodiments of the invention, Z and Z' in formulas (Ia)
and (Ib) as defined herein independently represent hydrogen
straight chain or branched C.sub.1-C.sub.4alkyl or benzyl. In a
preferred embodiment Z and Z' independently represent hydrogen,
methyl, ethyl, propyl, butyl, more preferably hydrogen, methyl or
ethyl. In a particularly preferred embodiment of the invention Z
and Z' are the same. Most preferably Z and Z' are the same and both
represent hydrogen, methyl or ethyl, most preferably methyl. In
some embodiments of the invention, the moiety Z--C--Z' represents a
5-, 6-, or 7-membered, preferably a 6-membered, cyclic or
heterocyclic group, which may be saturated or unsaturated. In
embodiments wherein said moiety represents a heterocyclic group, it
typically comprises one or more ring oxygen atoms, preferably one
ring oxygen atom. In some embodiments of the invention, the moiety
Z--C--Z' represents cyclohexyl.
As will be understood by those skilled in the art, the groups
represented by R, R', R.sup.a and R.sup.a' in formulas (Ia) and
(Ib) as defined herein comprise a functional group, represented by
Q, as well as a bridging aliphatic alkyl group comprising 1 to 8
carbon atoms, which may be branched or straight chain, denoted
`--(C.sub.1-C.sub.8alkyl)-`.
The term `functional group`, in the field of polymer engineering,
is generally understood to refer to a chemical moiety that is
capable of interacting with another group to form, typically, a
covalent or ionic bond. In preferred embodiments of the invention
Q, in the above definition of formulas (Ia) and (Ib), represents a
reactive group. The term "reactive group" as used herein refers to
a group that is capable of reacting with another chemical group to
form a covalent bond, i.e. is covalently reactive under suitable
reaction conditions, and generally represents a point of attachment
for another substance. Reactive groups generally include
nucleophiles, electrophiles and photoactivatable groups. In
preferred embodiments of the invention Q, in the above definition
of formulas (Ia) and (Ib), represents a reactive group selected
from amine, thiol, carboxyl, oxy, ethenyl, ethynyl, nitril,
cyanate, isocyanate, thiocyanate, isothiocyanate, imine, imide,
azide, nitrile, nitrite, nitro, nitroso, epoxide, cyclic carbonate,
oxazoline, anhydride, acrylate and chlorotriazine. In preferred
embodiments of the invention Q, in the above definition of formulas
(Ia) and (Ib), represents a reactive group selected from the group
consisting of epoxide and ethenyl.
In other preferred embodiments of the invention Q, in the above
definition of formulas (Ia) and (Ib), represents a reactive group
selected from hydroxyl, amine, thiol, carboxyl, oxy, ethenyl,
ethynyl, nitril, cyanate, isocyanate, thiocyanate, isothiocyanate,
imine, imide, azide, nitrile, nitrite, nitro, nitroso, epoxide,
cyclic carbonate, oxazoline, anhydride, acrylate and
chlorotriazine.
In other preferred embodiments of the invention Q, in the above
definition of formulas (Ia) and (Ib), represents a reactive group
selected from hydroxyl, amine, thiol, carboxyl, oxy, ethynyl,
nitril, cyanate, isocyanate, thiocyanate, isothiocyanate, imine,
imide, azide, nitrile, nitrite, nitro, nitroso, epoxide, cyclic
carbonate, oxazoline, anhydride, acrylate and chlorotriazine.
In preferred embodiments of the invention Q in the above definition
of formulas (Ia) and (Ib), represents a reactive group selected
from hydroxyl, amine, thiol, carboxyl, oxy, cyanate, isocyanate,
imine, imide, and oxazoline.
In preferred embodiments of the invention Q in the above definition
of formulas (Ia) and (Ib), represents a reactive group selected
from hydroxyl, amine, thiol, carboxyl, oxy, cyanate, isocyanate,
imine, imide, and oxazoline, most preferably hydroxyl.
The branched or straight chain aliphatic alkyl groups that are part
of the moieties represented by R, R', R.sup.a and R.sup.a' can
typically comprise up to 8 carbon atoms. For the avoidance of
doubt, it is to be noted that the indicated number of carbon atoms
concerns the total number of carbon atoms, i.e. it includes any
carbon atom that is not part of the main chain connecting X and Q
in the above formulas (Ia) and (Ib). In a preferred embodiment, the
alkyl groups are saturated. Furthermore, in a preferred embodiment,
the alkyl groups do not comprise any heteroatoms and/or non-alkyl
substituents. In certain preferred embodiments, the aliphatic alkyl
groups that are part of the moieties represented by R, R', R.sup.a
and R.sup.a' comprises 1 to 6 carbon atoms, more preferably 1 to 4
carbon atoms or 1 to 2 carbons atoms. In embodiments of the
invention R, R', R.sup.a and R.sup.a', in the above formulas (Ia)
and (Ib), independently represent a reactive group containing
moiety represented by the formula --(C.sub.1-C.sub.6alkyl)-Q,
preferably by the formula --(C.sub.1-C.sub.4alkyl)-Q, more
preferably by the formula --(C.sub.1-C.sub.2alkyl)-Q. In certain
preferred embodiments of the invention the branched or straight
chain aliphatic alkyl group that are part of the moieties
represented by R, R', R.sup.a and R.sup.a' are selected from the
group consisting methylene, ethylene, propylene, isopropylene and
butylene.
In a preferred embodiment of the invention bis-dioxolanes and
bis-dioxanes having a structure represented by formula (Ia) or (Ib)
are provided, wherein X represents a heteroatom or heteroatom
containing group independently selected from --O--, --NH-- and
--NR.sup.a--; X' represents a heteroatom or heteroatom containing
group independently selected from --O--, --NH-- and --NR.sup.a'--;
Z and Z' independently represent hydrogen, a straight chain or
branched C.sub.1-C.sub.4alkyl; and R, R', R.sup.a and R.sup.a'
independently represent a reactive group containing moiety
represented by the formula --(C.sub.1-C.sub.6alkyl)-Q, wherein
--C.sub.1-6alkyl represents a branched or straight chain aliphatic
alkyl group comprising 1 to 6 carbon atoms, and Q represents a
reactive group selected from hydroxyl, amine, thiol, carboxyl, oxy,
cyanate, isocyanate, thiocyanate, isothiocyanate, imine, imide,
epoxide, cyclic carbonate, oxazoline, anhydride and acrylate.
In a particularly preferred embodiment of the invention
bis-dioxolanes and bis-dioxanes having a structure represented by
formula (Ia) or (Ib) are provided, wherein: X represents a
heteroatom or heteroatom containing group independently selected
from --O--, --NH-- and --NR.sup.a--; X' represents a heteroatom or
heteroatom containing group independently selected from --O--,
--NH-- and --NR.sup.a'--; Z and Z' independently represent
hydrogen, a straight chain or branched C.sub.1-C.sub.2alkyl; and R,
R', R.sup.a and R.sup.a' independently represent a reactive group
containing moiety represented by the formula
--(C.sub.1-C.sub.4alkyl)-Q, wherein --C.sub.1-4alkyl represents a
branched or straight chain aliphatic alkyl group comprising 1 to 4
carbon atoms, and Q represents a reactive group selected from
hydroxyl, amine, thiol, carboxyl, oxy, cyanate, isocyanate, imine,
imide, and oxazoline.
As will be evident to those of average skill in the art, the
present bis-dioxolanes and bis-dioxanes comprise numerous centers
of chirality. The invention is not particularly limited with regard
to the orientation of these chiral centers. Nonetheless, in
accordance with the invention, it is particularly preferred to
produce the present bis-dioxolanes and bis-dioxanes from biomass
sources, as is explained in more detail herein elsewhere, and there
is a particular configuration that is inherent to such compounds as
obtained from biomass sources.
Hence, in preferred embodiments of the invention, a bis-dioxolane
as defined herein is provided, having the structure represented by
formula (IIa):
##STR00003## wherein R, R', X, X' and Z all have the same meaning
as defined herein elsewhere in relation to formula (Ia).
In other embodiments of the invention, a bis-dioxane as defined
herein is provided, having the structure represented by formula
(IIb) or (IIc):
##STR00004## wherein R, R', X, X' and Z all have the same meaning
as defined herein elsewhere in relation to formula (Ib).
In certain embodiments of the invention, bis-dioxolanes are
provided having the structure represented by any of formulas
(IIIa)-(IIIh) as depicted below. The bis-dioxolanes having the
structure represented by formulas (IIIb), (IIId), (IIIe), (IIIf),
(IIIg) and (IIIh) represent particularly preferred examples of the
present invention, of which the bis-dioxolanes having the structure
represented by formulas (IIIe), (IIIf) and (IIIg) stand out in
particular.
##STR00005## ##STR00006##
A second aspect of the invention, concerns a method of producing a
bis-dioxolane or bis-dioxane as defined herein, said method
comprising the steps of
a) providing a source of a C6 aldaric acid;
b) derivatization of the C6 aldaric acid by combining the source of
the C6 aldaric acid with a lower alkyl alcohol under conditions
that cause the lower alkyl alcohol to react with the C6 aldaric
acid carboxyl groups to form lower alkyl ester moieties;
c) acetalisation of the esterified C6 aldaric acid as obtained in
step b) by combining it with an acetalisation reagent, selected
from the group of compounds having the formula Z--C(.dbd.O)--Z',
wherein Z and Z' have the same meaning as defined in relation to
formulas (Ia) and (Ib), and the corresponding di-alkoxyacetals and
di-alkoxyketals, under conditions that cause the acetalisation
reagent to react with the aldaric acid hydroxyl groups to form the
corresponding bis-diox(ol)anes; d) conversion of the
bis-diox(ol)anes obtained in step c) by reaction with a hydroxyl or
amine reagent, selected from the group consisting of
Q-(C.sub.1-C.sub.8alkyl)-OH; Q-(C.sub.1-C.sub.8alkyl)-NH.sub.2 and
Q-(C.sub.1-C.sub.8alkyl)-NH--(C.sub.1-C.sub.8alkyl)-Q, wherein Q
and C.sub.1-C.sub.8alkyl have the same meaning as defined in
relation to formulas (Ia) and (Ib), under conditions that cause the
hydroxyl or amine reagent to displace the lower alkyl groups of the
ester moieties of the bis-diox(ol)anes to form a bi-functional or
polyfunctional bis-diox(ol)ane of the invention.
As will be understood by those skilled in the art, in accordance
with the invention it is preferred that starting compound for the
process of the invention is derived from a biomass source. For that
reason, it is particularly preferred that the C6 aldaric acid is
galactaric acid. Embodiments are however also envisaged wherein the
C6 aldaric acid is mannaric acid or glucaric acid. The present
inventors have observed that the use of galactaric acid as the
starting compound in the processes of the invention yields the
corresponding bis-dioxolane, i.e. the 2,3;4,5-diacetal, as defined
herein, whereas the use of mannaric acid or glucaric acid yields
the corresponding bis-dioxane, i.e. the 2,4;3,5-diacetal, as
defined herein. Without wishing to be bound by any theory, the
inventors believe that one form is energetically highly favoured
over the other.
In the context of the present invention, a `source of C6 aldaric
acid` can be any composition containing substantial amounts of the
C6 aldaric acid, typically as the major component. In embodiments
of the invention, the source of C6 aldaric acid comprises more than
90 wt. %, based on dry solids weight, of C6 aldaric acid, more
preferably more than 95 wt. %, more than 96 wt. %, more than 97 wt.
%, more than 98 wt. %, more than 99 wt. % of C6 aldaric acid. In
some embodiments the source of C6 aldaric acid comprises
substantially or completely pure C6 aldaric acid. In some
embodiments of the invention, step a) comprises providing a
solution of C6 aldaric acid in a solvent in which the
derivatization according to step b) can conveniently be carried
out.
As already explained herein, it is particularly preferred in
accordance with the invention that the bis-diox(ol)ane compounds
are produced from a renewable source, in particular from a biomass
source.
In accordance with one embodiment, suitable biomass sources include
those containing substantial quantities of galacturonic acid, such
as hemicellulosic and pectin rich biomass. Materials may
accordingly be utilized that, at present, are still mainly
considered by-products in various industries. Turning such
by-products into a new natural resource, is obviously an advantage.
In preferred embodiments of the invention, the hemicellulose and
pectin rich biomass is sugar beet pulp, which constitutes the
production residuum from the sugar beet industry. The production of
galactaric acid from hemicellulose and pectin rich biomass involves
the extraction of galacturonic acid and subsequent conversion of
galacturonic acid into galactaric acid by selective oxidation of
the terminal hydroxyl group. A highly efficient process for the
oxidative conversion of galacturonic acid to galactaric acid, has
recently been disclosed in international patent applications WO
2013/151428 and WO 2016/056907, the contents of which are
incorporated herein by reference.
As indicated herein, step b) comprises combining the source of the
C6 aldaric acid with a lower alkyl alcohol under conditions that
cause the alcohol to react with the C6 aldaric acid carboxyl groups
to form lower alkyl ester moieties.
Suitable examples of lower alkyl alcohols include methanol,
ethanol, propanol and isopropanol. Methanol and ethanol are
preferred. Most preferably, the lower alkyl alcohol is ethanol.
In accordance with preferred embodiments of the present invention,
step b) is carried out in the presence of a suitable catalyst.
Suitable catalysts include acid The use of sulfuric acid is
particularly preferred.
Examples of suitable solvents for carrying out step b) include
alcohols. The use of ethanol is particularly preferred.
It is within the routine of those of average skill in the art to
determine the appropriate conditions for carrying out the process
and to optimize it in terms of yield, efficiency, etc.
As indicated herein, step c) comprises combining the esterified
aldaric acid obtained in step b) with an acetalisation reagent
under conditions that cause the acetalisation reagent to react with
the aldaric acid hydroxyl groups to form the corresponding
bis-diox(ol)ane.
The acetalisation reagent is an aldehyde or a ketone containing
lower alkyl compound having the formula Z--C(.dbd.O)--Z', with Z
and Z' being as defined in relation to formulas (Ia) and (Ib)
above. It is also feasible to use the corresponding
di-alkoxyacetals and di-alkoxyketals, where the oxo group of the
aldehyde or ketone has been converted into a di-alkoxy moiety.
Typically these di-alkoxyacetals and di-alkoxyketals have the
general formula Z--C(OR.sup.bOR.sup.b')--Z', with Z and Z' being as
defined in relation to formulas (Ia) and (Ib) and R.sup.b and
R.sup.b' representing lower alkyl, typically methyl or ethyl, most
preferably methyl.
In a particularly preferred embodiment of the invention, the
acetalisation reagent is selected from the group consisting of
formaldehyde, acetaldehyde, acetone, propanal, butanone, butanal,
cyclohexanone, benzaldehyde and the corresponding dialkoxylated,
preferably dimethoxylated, acetals or ketals thereof. Most
preferably the acetalisation reagent is 2,2-dimethoxypropane.
The acetalisation is typically carried out in the presence of a
suitable catalyst. Suitable catalysts include acid The use of
p-toluene-sulfonic acid is particularly preferred.
Suitable solvents include. Acetone, methylene chloride The use of
methylene chloride is particularly preferred.
It is within the routine of those of average skill in the art to
determine the appropriate conditions for carrying out the process
and to optimize it in terms of yield, efficiency, etc.
Additionally, processes of producing bis-diox(ol)ane compounds from
aldaric acids have been described in the art. For illustrative
purposes, Promper et al. (Green Chem, 2006, 8, 467-478) and
Munoz-Guerra et al. (Green Chem, 2014, 16, 1716-1739) may be
referred to in this regard.
As indicated herein, step d) comprises reacting the bis-diox(ol)ane
as obtained in step c) with a hydroxyl or amine reagent under
conditions that cause the hydroxyl or amine containing reactant to
displace the lower alkyl groups of the ester moieties of the
bis-diox(ol)anes to form the bi-functional or polyfunctional
bis-diox(ol)ane compounds of the invention.
The hydroxyl or amine reagent is typically selected from the group
consisting of Q-(C.sub.1-C.sub.8alkyl)-OH;
Q-(C.sub.1-C.sub.8alkyl)-NH.sub.2 and
Q-(C.sub.1-C.sub.8alkyl)-NH--(C.sub.1-C.sub.8alkyl)-Q, wherein Q
and C.sub.1-C.sub.8 alkyl have the same meaning as defined in
relation to formula (I). As will be understood by those of ordinary
skill in the art, the precise structure of the hydroxyl or amine
reagent depends mainly on the functional group(s) that are desired
in the bi- or polyfunctional bis-diox(ol)ane. The bis-diox(ol)ane
compound as obtained in step c) of the present process can be
reacted with a very wide variety of hydroxyl and amine containing
reactants according to this invention, with invariably high
efficiency and selectivity, which constitutes one of the
significant advantages of the present invention.
The reaction is typically carried out by combining the
bis-diox(ol)ane as obtained in step c) with the hydroxyl or amine
containing reactant in a suitable solvent and applying conditions
under which the displacement occurs. In case the target product is
the allyl ester, the displacement reaction involves an equilibrium
between the starting lower alkyl esters and the target derivative.
This equilibrium can be driven towards the target compound by using
an excess amount of the alcohol. In case the target product is the
allyl amide derivative, this target product is in fact the
energetically favoured product.
Hence, in certain embodiments of the invention processes as defined
herein are provided for producing a compound according to formulas
(Ia) and (Ib) wherein X and X' represent --O-- and step d)
comprises:
d1) combining the bis-diox(ol)ane with a stoichiometric excess of a
hydroxyl containing reactant having the formula
Q-(C.sub.1-C.sub.8alkyl)-OH, optionally in a suitable solvent, to
produce a liquid reaction mixture;
d2) subjecting the liquid reaction mixture to conditions under
which the displacement reaction proceeds.
Suitable solvents include C1-C8 alcohols containing the required
functional end groups, C1-C4 containing the required functional end
groups The use of allyl alcohol is particularly preferred.
The transesterification reaction is typically carried out by
contacting the bis-diox(ol)ane product with an excess of one of the
above mentioned alcohols in the presence of a suitable alkaline
catalyst. Suitable alkaline catalysts include sodium alkoxide,
sodium hydroxide, sodium carbonate, strong alkaline resins The use
of sodium methoxide is particularly preferred.
The molar ratio of the hydroxyl containing reactant to the
bis-diox(ol)ane is typically in excess of the stoichiometric ratio.
In particular, the molar ratio of the hydroxyl containing reactant
to the bis-diox(ol)ane may be in the range of 3 to 100, preferably
5 to 80, more preferably 10 to 60.
It is within the routine of those of average skill in the art to
determine the appropriate conditions for carrying out the process
and to optimize it in terms of yield, efficiency, etc.
The process may conveniently be carried out in a batch reactor,
such as a continuous stirred tank reactor (CSTR). The reaction is
typically carried out at a temperature and pressure and for a
contact time sufficient to effect the formation of the target ester
derivative. In certain embodiments of the invention, the reaction
is carried out under reflux conditions. In certain embodiments of
the invention, step d2) comprises subjecting the liquid reaction
mixture to temperatures within the range of 20.degree. C. to
120.degree. C., preferably within the range of 30 to 100.degree.
C., preferably within the range of 40-90.degree. C., more
preferably within the range of 50-85.degree. C., and most
preferably within the range of 60-80.degree. C. In certain
embodiments of the invention, step d2) comprises subjecting the
liquid reaction mixture to a pressure within the range of 0.01-10
Bar, preferably within the range of 0.05-5 Bar, more preferably
within the range of 0.05-3 Bar The reaction is carried for a period
of time sufficient to effect conversion under the chosen
conditions. The reaction time can typically range from several
hours to a number of days, typically from 3 hours to 125 hours,
most preferably from 10-100 hours. Conversion of the
bis-diox(ol)ane into the target compound is preferably from about
20% to about 100% and most preferably from about 60% to about 100%.
Selectivity for the target bis-diox(ol)ane, is preferably from
about 20% to 100% and most preferably from about 60% to 100%.
Alternatively, in certain embodiments of the invention processes as
defined herein are provided for producing bis-diox(ol)anes
according to formulas (Ia) and (Ib) wherein X and X' represent
--NH--, --NR.sup.a-- or --NR.sup.a'--, and step d) comprises: d1')
combining the bis-diox(ol)ane with stoichiometric excess of the
amine containing reactant selected from the group consisting of
Q-(C.sub.1-C.sub.8alkyl)-NH.sub.2 and
Q-(C.sub.1-C.sub.8alkyl)-NH--(C.sub.1-C.sub.8alkyl)-Q in a suitable
solvent, to produce a liquid reaction mixture; d2') subjecting the
liquid reaction mixture to conditions under which the displacement
reaction proceeds.
Suitable solvents according to these embodiments include methanol
and ethanol. The use of ethanol is particularly preferred.
The molar ratio of the amine containing reactant to the
bis-diox(ol)ane is typically in slight excess of the stoichiometric
ratio. In preferred embodiments, the molar ratio of the amine
containing reactant to the bis-diox(ol)ane may be in the range of
2.01-10, preferably 2.05-5, more preferably 2.1-2.5.
Step d1') and d2') may conveniently be carried out in a batch
reactor, such as a CSTR. The reaction is typically carried out at a
temperature and pressure and for a contact time sufficient to
effect the formation of the ester/amide moieties. In certain
embodiments of the invention, the reaction is carried out under
reflux conditions. In certain embodiments of the invention, step
d2') comprises subjecting the liquid reaction mixture to
temperatures within the range of 20.degree. C. to 120.degree. C.,
preferably within the range of 20 to 100.degree. C., preferably
within the range of 20-90.degree. C., more preferably within the
range of 20-85.degree. C., and most preferably within the range of
20-80.degree. C. In certain embodiments of the invention, step d2')
comprises subjecting the liquid reaction mixture to a pressure
within the range of 0.01-10 Bar, preferably within the range of
0.05-5 Bar, more preferably within the range of 0.05-3 Bar The
reaction is carried out for a period of time sufficient to effect
conversion under the chosen conditions. The reaction time can range
from several minutes to a number of days, typically from 30 minutes
to 50 hours, most preferably from 3-24 hours. Conversion of the
bis-diox(ol)ane into the target compound is preferably from about
20% to about 100% and most preferably from about 60% to about 100%.
Selectivity for the target bis-diox(ol)ane, is preferably from
about 20% to 100% and most preferably from about 60% to 100%.
In certain embodiments of the invention, step d2) or d2') may be
followed by a step d3) comprising the separation and/or isolation
of the bis-diox(ol)ane from the reaction mixture, by any suitable
technique known by the person skilled in the art, such as
chromatographic separation and/or crystallization. Embodiments are
also envisaged, wherein the reaction mixture produced in step d2)
is immediately used for further conversion reactions, e.g.
additional displacement reactions, as will be illustrated in the
examples, wherein allyl esters and allyl amides according to
formulas (Ia) and (Ib) are converted to epoxy esters and epoxy
amides according to formulas (Ia) and (Ib) respectively. For
instance, the allyl ester of formula (IIIa) can be converted to the
epoxy ester of formula (IIIb) and the allyl amide of formula (IIIc)
can be converted to the epoxy amide of formula (IIId).
Alternatively, the epoxy esters according to formulas (Ia) and (Ib)
can be produced by first converting an aldaric acid into the
corresponding di-carboxylic bis-diox(ol)ane and subsequently
reacting said di-carboxylic bis-diox(ol)ane with epichlorohydrin,
which is preferably a biobased.
A further aspect of the invention, concerns compounds and
composition as obtained and/or obtainable by the methods defined
herein. Such compounds and/or compositions may be the same or may
differ in some aspect(s) from compounds and/or compositions as
described herein.
A further aspect of the invention concerns the use of the bi- or
polyfunctional bis-diox(ol)ane as defined herein and/or as
obtainable by the methods as defined herein for the production
and/or modification of polymer materials. In a particularly
preferred embodiment of the invention, said use involves production
and/or modification processes that are performed in an aqueous
solvent.
In an embodiment of the invention, the use of the bi- or
polyfunctional bis-diox(ol)ane as defined herein and/or as
obtainable by the methods as defined herein is provided as a
polymer cross-linking and/or for cross-linking polymers. In a
particularly preferred embodiment of the invention, said use
involves the cross-linking of polymers in an aqueous solvent.
In an embodiment of the invention, the use of the bi- or
polyfunctional bis-diox(ol)ane as defined herein and/or as
obtainable by the methods as defined herein is provided as a
coupling agent in polymer composite materials and/or for producing
and/or modifying polymer composite materials. In a particularly
preferred embodiment of the invention, said use involves the
coupling and/or production and/or modification of polymer
composites in an aqueous solvent.
In an embodiment of the invention, the use of the bi- or
polyfunctional bis-diox(ol)ane as defined herein and/or as
obtainable by the methods as defined herein is provided as a
polymer building block and/or for building polymers.
The types of polymers that can be produced and/or modified using
the bi- or polyfunction dioxolane compounds of the invention is
virtually limitless as a large variety of functional groups can be
incorporated. To name just a few exemplary materials wherein the
present bi- of polyfunction bis-diox(ol)anes have particular
utility, polyesters, polyurethanes and polycarbonates.
The present invention has been described above with reference to a
number of exemplary embodiments as shown in the drawings.
Modifications and alternative implementations of some parts or
elements are possible, and are included in the scope of protection
as defined in the appended claims.
EXAMPLES
Example 1: Synthesis of GalX-allylester
Sodium methoxide (0.16 g, 2.9 mmol) was added to a solution of GalX
(20.0 gram, 57.8 mmol, obtained following procedures described in
literature, allyl alcohol (250 mL). The solution was refluxed for 5
days. After cooling down and evaporation, the solid material was
stirred in heptane and filtrated to remove the salts. The product
was isolated after evaporation of heptanes, followed by
crystallization from ethanol and water, filtrated and dried in a
vacuum oven.
Product GalX-allylester (Mw 370): 15.4 gram (yield 72%). HPLC: 99%
pure material. .sup.1H NMR (400.17 MHz, CDCl.sub.3): .delta.
(ppm)=5.92 (m, 2H); 5.36 (dd, .sup.2J.sub.HH=17.2 Hz,
.sup.3J.sub.HH=1.4 Hz, 2H); 5.27 (dd, .sup.2J.sub.HH=10.4 Hz,
.sup.3J.sub.HH=1.2 Hz, 2H); 4.69 (d, .sup.3J.sub.HH=5.85 Hz, 4H);
4.62 (dd, .sup.2J.sub.HH=4.3 Hz, .sup.3J.sub.HH=1.3 Hz, 2H); 4.49
(dd, .sup.2J.sub.HH=4.2 Hz, .sup.3J.sub.HH=1.3 Hz, 2H); 1.49 (s,
6H); 1.44 (s, 6H). .sup.13C NMR (100.62 MHz, CDCl.sub.3): .delta.
(ppm)=170.74 (C.dbd.O); 131.45 (CH.sub.2.dbd.CH); 119.30
(CH.sub.2.dbd.CH); 112.53 (C(CH.sub.3).sub.2); 79.28 (CHCH); 76.13
(C.dbd.OCHCH); 66.22 (CH.sub.2OC.dbd.O); 27.15 (CCH.sub.3); 26.12
(CCH.sub.3).
TABLE-US-00001 Mw Density Quantity Quantity Quantity eq Compound
(g/mol) (g/ml) (g) (ml) (mmol) 1 GalX 346 -- 20.0 -- 57.8
Allylalcohol 58.1 0.854 250 0.2 Sodium 54.0 -- 0.63 -- 11.6
methoxide (NaOMe) 1 GalX- 370 -- 21.4 -- 57.8 allylester
##STR00007##
Example 2: Synthesis of GalX-diepoxyester
mCPBA (35.8 g, 208 mmol) was added to a solution of GalXallylester
(11 gram, 29.7 mmol) in DCM (250 mL). The solution was stirred for
60 hours at reflux temperature. After cooling down, the solution
was filtrated. The filtrate was washed with Na.sub.2SO.sub.3,
Na.sub.2CO.sub.3 and water. The organic phase was evaporated to
dryness. Product GalX-diepoxyester crude (Mw 402): 8.8 gram (yield
74%). HPLC: 99% pure material. .sup.1H NMR (400.17 MHz,
CDCl.sub.3): .delta. (ppm)=4.61 (d, .sup.3J.sub.HH=4.4 Hz, 2H);
4.50 (dt, .sup.2J.sub.HH=12.2 Hz, .sup.3J.sub.HH=2.5 Hz, 2H); 4.46
(dd, .sup.2J.sub.HH=4.4 Hz, .sup.3J.sub.HH=1.3 Hz, 2H); 4.04 (ddd,
.sup.2J.sub.HH=12.2 Hz, .sup.3J.sub.HH=6.2 Hz, .sup.4J.sub.HH=1.1
Hz, 2H); 3.20 (m, 2H); 2.81 (t, .sup.2J.sub.HH=4.8 Hz, 2H); 2.64
(dd, .sup.2J.sub.HH=4.9 Hz, .sup.3J.sub.HH=2.5 Hz, 2H); 1.47 (s,
6H); 1.42 (s, 6H). .sup.13C NMR (100.62 MHz, CDCl.sub.3): .delta.
(ppm)=170.79 (C.dbd.O); 112.53 (C(CH.sub.3).sub.2); 79.28 (CHCH);
76.13 (C.dbd.OCHCH); 65.90 (CH.sub.2OC.dbd.O); 49.02 (CHO); 44.62
(CH.sub.2O); 27.15 (CCH.sub.3); 26.12 (CCH.sub.3).
TABLE-US-00002 Mw Density Quantity Quantity Quantity eq Compound
(g/mol) (g/ml) (g) (ml) (mmol) 1 GalXallylester 370 -- 11.0 -- 29.7
7 Meta- 172 -- 35.8 -- 208 chloroperoxybenzoic- acid (mCPBA) --
Dichloromethane -- -- -- 250 ml -- (DCM) 1 GalX-diepoxyester 402 --
11.9 -- 29.7
##STR00008##
Example 3: Synthesis of GalX-allylamide
Allylamine (g, 30.3 mmol) was added to a solution of GalX (5 gram,
14.5 mmol) in MeOH (50 mL). The solution was stirred for 1 night at
room temperature. After evaporation of the solvent, 50 mL of ethyl
acetate was added and the solution was refluxed overnight. After
cooling down and evaporation, the solid material was crystallized
from ethanol and water, filtrated and dried in a vacuum oven.
Product GalX-allylamide (Mw 368): 3.1 gram (yield 58%). HPLC: 99%
pure material. .sup.1H NMR (400.17 MHz, CDCl.sub.3): .delta.
(ppm)=6.74 (s, 2H); 5.83 (m, 2H); 5.21 (dd, .sup.2J.sub.HH=17.2 Hz,
.sup.3J.sub.HH=1.4 Hz, 2H); 5.15 (dd, .sup.2J.sub.HH=10.2 Hz,
.sup.3J.sub.HH=1.2 Hz, 2H); 4.79 (d, .sup.2J.sub.HH=7.0 Hz, 2H);
4.53 (d, .sup.2J.sub.HH=7.1 Hz, 2H); 3.91 (m, 4H), 1.51 (s, 6H),
1.44 (s, 6H). .sup.13C NMR (100.62 MHz, CDCl.sub.3): .delta.
(ppm)=170.72 (C.dbd.O); 133.82 (CH.sub.2.dbd.CH); 116.69
(CH.sub.2.dbd.CH); 110.89 (C(CH.sub.3).sub.2); .delta. 78.76
(CHCH); 75.01 (C.dbd.OCHCH); .delta. 41.35 (CH.sub.2NHC.dbd.O);
26.82 (CCH.sub.3); 26.11 (CCH.sub.3).
TABLE-US-00003 Mw Density Quantity Quantity Quantity eq Compound
(g/mol) (g/ml) (g) (ml) (mmol) 1 GalX 346 -- 5 -- 14.5 2.1
Allylamine 57.1 0.763 1.73 2.27 30.3 -- MeOH -- -- -- 50 ml -- 1
GalX- 368 -- -- 14.5 allylamide
##STR00009##
Example 4: Synthesis of GalX-diepoxyamide
mCPBA (32.7 g, 190 mmol) was added to a solution of GalXallylamide
(10 gram, 27.2 mmol) in DCM (250 mL). The solution was stirred for
60 hours at reflux temperature. After cooling down, the solution
was filtrated. The filtrate was washed with Na.sub.2SO.sub.3,
Na.sub.2CO.sub.3 and water. The organic phase was evaporated to
dryness.
Product GalX-diepoxyamide crude (Mw 402): 7.1 gram (yield 65%);
HPLC: 99% pure material.
TABLE-US-00004 Mw Density Quantity Quantity Quantity eq Compound
(g/mol) (g/ml) (g) (ml) (mmol) 1 GalXallylamide 368 -- 10.0 -- 27.2
7 Meta- 172 -- 32.7 -- 190 chloroperoxybenzoic- acid (mCPBA) --
Dichloromethane -- -- -- 250 ml -- (DCM) 1 GalX- 402 -- 10.9 --
27.2 diepoxyamide
##STR00010##
Example 5: Synthesis of GalX-diethanolamide
Ethanolamine (43.5 ml, 0.72 mol) was added to a solution of GalX
(100 gram, 0.29 mol) in EtOH (500 mL). The solution was stirred for
1 night at reflux temperature. After evaporation of the solvent,
the solid material was recrystallized from ethylacetate (1 L),
filtrated and dried in a vacuum oven.
Product GalX-di-ethanolamide (Mw 376): 83.6 gram (yield 77%). HPLC:
99% pure material. .sup.1H NMR (400 MHz, DMSO-d.sub.6) .delta. 7.82
(t, J=5.8 Hz, 2H), 4.68 (t, J=5.5 Hz, 2H), 4.51 (dd, J=6.3 Hz, 2H),
4.36 (dd, 2H), 3.43 (q, J=6.1 Hz, 4H), 3.29-3.10 (m, 4H), 1.41 (s,
6H), 1.35 (s, 6H). The water-solubility of the product is
approximately 25 wt. % (35 gram per 100 ml water, at ambient
temperature).
TABLE-US-00005 Mw Density Quantity Quantity Quantity eq Compound
(g/mol) (g/ml) (g) (ml) (mol) 1 GalX 346.38 -- 100 g -- 0.29 2.5
Ethanolamine 61.08 1.012 44 g 43.5 ml 0.72 -- MeOH -- -- -- 1000 ml
-- 1 GalX-di- 376.41 -- 108.6 g -- 0.29 ethanolamide
##STR00011##
Example 6: Synthesis of GalX-di-(di-ethanolamide)
Di-ethanolamine (9.1 ml, 94.6 mmol) was added to a solution of GalX
(15 gram, 43 mmol) in EtOH (75 mL). The solution was stirred for 1
night at reflux temperature. After evaporation of the solvent, the
material was recrystallized from ethylacetate (150 mL), filtrated
and dried in a vacuum oven.
Product GalX-di-ethanolamide (Mw 376): 12.6 gram (yield 63%). HPLC:
99% pure material. .sup.1H NMR (400 MHz, DMSO-d.sub.6) .delta. 4.80
(t, J=5.3 Hz, 2H), 4.70 (dd, 2H), 4.67 (t, J=5.4 Hz, 2H), 4.61 (dd,
J=3.8, 1.8 Hz, 2H), 3.72-3.60 (m, 2H), 3.60-3.51 (m, 4H), 3.51-3.39
(m, 7H), 3.36-3.21 (m, 3H), 1.32 (s, 6H), 1.27 (s, 6H). The
water-solubility of the product was approximately 50 wt. % (i.e.
100 gram per 100 ml water, at ambient temperature).
TABLE-US-00006 Mw Density Quantity Quantity Quantity eq Compound
(g/mol) (g/ml) (g) (ml) (mmol) 1 GalX 346.38 -- 15 -- 43 2.2
Diethanolamine 105.14 1.09 9.9 9.1 ml 94.6 -- EtOH -- -- -- 75 ml
-- 1 GalX-di- 464.51 -- 20 -- 43 (diethanolamide)
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